Background: The effects of off-pump coronary artery bypass (OPCAB) surgery on endothelial cell activation are poorly understood. Endothelial cell adhesion molecules (CAMs) are expressed and released when the endothelium is activated. We compared plasma CAMs (E-selectin, ICAM-1 and VCAM-1) and HUVEC expression of the same CAMs when exposed to plasma taken before, during and after OPCAB or on-pump coronary surgery (CABG). Methods: Patients undergoing first time CABG (n=10) or OPCAB (n=10) had 6 blood samples taken before surgery and up to 24. h post-operatively. Plasma samples were assayed for E-selectin, ICAM-1 and VCAM-1. The same plasma samples were exposed to HUVEC cultures and cell-surface expression of E-selectin, ICAM-1 and VCAM-1 measured. Data are expressed as mean ± SEM of n subjects. Results: Plasma E-selectin was unchanged. Plasma ICAM-1 and VCAM-1 were elevated 24. h post-operatively in both groups (P<0.01), with no differences between the groups. Twenty-four hours post-OPCAB plasma increased basal and IL-1β induced expression of endothelial VCAM-1 by 133 ± 16% and 140 ± 27% (P<0.05), respectively. Plasma taken 3. h post-CABG decreased endothelial VCAM-1 expression by 76 ± 10% (P<0.05). Peri-operative plasma had no effect on endothelial expression of E-selectin or ICAM-1 in either group. Conclusions: OPCAB and CABG with CPB appear to generate qualitatively different inflammatory responses with respect to endothelial activation, which may have clinical implications.